Why Pediatricians Care about Finding a GERD Gene[This article first appeared in the PAGER newsletter, Reflux Digest, October 2003]

When you talk about genetic discoveries, many people tune out. When they hear about genetic diseases, they think of dying children, gene therapy or abortion. Not pleasant topics.

But genetics has progressed a long way and the information gathered from genetic studies can improve the practice of regular medicine.

For pediatricians, one of the most frustrating things about having patients with GER symptoms is deciding who needs treatment and which treatment to try first. We hope that our genetic discoveries will eventually take some of the guess work out of diagnosing GERD and finding the right treatment for each child.

Here is an imaginary pediatric appointment in the future. It shows how our genetic study MAY have an impact.

Mr. and Mrs. Smith bring their crying baby boy into the pediatrician. They know all about reflux because they downloaded 3-D videos from the SuperInternet. They believe their son has reflux but his symptoms vary a lot from day to day. They can’t see any pattern and they don’t know whether their worry is warranted.

Dr. Doe listens closely to the parents and ask a lot of questions about little Johnny’s symptoms. He also asks about any blood relatives who have digestive problems, allergies or symptoms similar to little Johnny’s. The exam shows this baby’s weight gain is not great.

Dr. Doe is proud of his ability to guess which type of reflux each child has and in this case he suspects “Milk Soy Protein Intolerance Reflux” or “Cows Milk Allergy Reflux” Just to be sure, he has little Johnny suck on the stylus from his PDA which has recently been upgraded with SuperWhopperGeneOMaticMark IV gene analysis software. The stylus collects a saliva sample.

Minutes later Dr. Doe is able to tell the Smith’s that little Johnny has “Temporary Protein Intolerance Reflux of Infancy” [future term] and needs to be on an amino acid based formula and avoid most whole proteins, not just milk. He is also able to assure them that Johnny doesn’t have the rare mutation for “Chronic Protein Intolerance Reflux” [future term] that leads to a lifelong need for special formulas. He will only need to stay on the diet for a year and then they can try weaning.

Since “Temporary Protein Intolerance Reflux of Infancy” is now an official disease with an official test, the special medical formulas are covered by the National Health Insurance Office: Health Assurance and Hospital Alliance (HAHA). Dr. Doe’s PDA has already placed the order and a case of formula will arrive at the Smith’s house tomorrow.

Dr. Doe explains his findings and choice of treatment to the family. He also zaps a file with custom home care instructions and a diet for Johnny to the Smith’s PDA so they can study it at their convenience and share it with babysitters and relatives.

Is this story bad humor? Yes! It is wishful thinking? Yes! Is it impossible science fiction? Maybe not. But we have a LONG way to go.

Long before your doctor has their own SuperWhopperGeneOMaticMark IV, the genetic discoveries will help us officially sub-type the disease. Already doctors who see many children with reflux are identifying clinical patterns that divide the disease into rough categories like “immaturity reflux” and “allergic reflux.”Diseases like Hepatitis C are already being genetically sub-typed to match the patient with the best treatment. (See http://www.toshiba. co.jp/about/press/2001_10/pr1801.htm )

Let’s work together to make this possible for GERD. Here are the steps we need to take to make the story above a reality:

1. √Find families with many affected members. Find researchers who want to study them.2. √Use family trees to document inheritance patterns.3. √Collect samples and look for known genetic markers.4. √Identify the most likely chromosome for GERD gene (ch. 13).5. √Analyze the family samples to narrow the search area (region q14). [THE GERD GENE IS "MAPPED"]6. √Using data from the Human Genome Project and other genetic databases, compile a list of all of the DNA sequences of every known and novel gene located in 13q14.7. Search for errors (mutations) in the DNA sequences of all the genes located in the GERD map region in patients from multiple GERD families. When a mutation is found in one particular gene from affected, but not unaffected members of GERD families, this will be the first GERD gene. [1ST GERD GENE IS IDENTIFIED]8. Invent a genetic test to compliment clinical judgement and current testing9. Determine the normal function of the non-mutated GERD gene.10. Figure out how the mutated form of this gene malfunctions. [UNDERSTAND HOW 1st GERD GENE CAUSES GERD] 11. Find more families with inherited GERD to search for additional GERD genes. (We know there is more than one cause.)12. Compare various mutations in the GERD genes to symptom patterns and responsiveness to drugs. [TARGET CURRENT DRUGS TO INDIVIDUALS]13. Use information about the GERD genes to find more biochemical pieces of the GERD puzzle.14. Based on a detailed understanding of its several causes, write a complete biochemical "instruction manual" for diagnosing, preventing, and curing all forms of GERD.15. Develop rational drugs that do more than mask the symptoms of GERD for children and adults. [NO MORE SUFFERING!]

Our wonderful research team is currently working on step 7 and they need to find more families to make the dream come true.

What YOU can do

If you are a professional who treats children with GERD, please ask your patients about other family members who might have GERD. In today’s mobile society, it is easy to miss this connection unless you ask. Please tell them about the study. Your patients may be thrilled to make a scientific contribution by participating in the study.

If your family already signed up and has never been contacted, please get in touch again. The researchers have now found a way to use smaller families that don’t have a dozen affected members and multiple generations to study.

Contact rpreston@wpahs.org and call 888-887-7729. You can also fill out the survey on www.reflux.org